TLR agonists and/or IL-15 adjuvanted mucosal SIV vaccine reduced gut CD4+ memory T cell loss in SIVmac251-challenged rhesus macaques

Adjuvant plays an important role in increasing and directing vaccine-induced immune responses. In a previous study, we found that a mucosal SIV vaccine using a combination of IL-15 and TLR agonists as adjuvant mediated partial protection against SIVmac251 rectal challenge, whereas neither IL-15 nor TLR agonists alone as an adjuvant impacted the plasma viral loads. In this study, dissociation of CD4+ T cell preservation with viral loads was observed in the animals vaccinated with adjuvants. Significantly higher levels of memory CD4+ T cell numbers were preserved after SIVmac251 infection in the colons of the animals vaccinated with vaccine containing any of these adjuvants compared to no adjuvant. When we measured the viral-specific CD8+ tetramer responses in the colon lamina propria, we found significantly higher levels of gag, tat, and pol epitope tetramer+ T cell responses in these animals compared to ones without adjuvant, even if some of the animals had similarly high viral loads. Furthermore, this CD4+ T preservation was positively correlated with increased levels of gag and Tat, but not pol tetramer+ T cell responses, and inversely correlated with beta-chemokine expression. The pre-challenged APOBEC3G expression level, which has previously been shown inversely associated with viral loads, was further found positively correlated with CD4+ T cell number preservation. Overall, these data highlight one unrecognized role of adjuvant in HIV vaccine development, and show that vaccines can produce a surprising discordance between CD4+ T cell levels and SIV viral load.